tbuckley/cabot-search huggingface dataset:
Abstract 10976: Midlife Caregivers: At Risk for Cardiovascular Disease?
Authors: Jennifer Smith, Carlie Fleming, Joel G Anderson
Journal: Circulation (2022)

Introduction: Caregivers remain an invisible population that may be at increased risk for cardiovascular disease (CVD) secondary to the additional stress of caregiving. Some groups of caregivers demonstrate as much as an 82% increased risk of CVD compared with non-caregivers. Purpose/Hypothesis: The purpose of this study was to describe characteristics of midlife caregivers from a large, publicly available dataset and to identify CVD risk factors among a subset of these caregivers. Methods: This was a secondary analysis of data from the Midlife in the United States (MIDUS) study. The sample was limited to participants who reported caring for someone else. Data were collected using sociodemographic questionnaires and survey instruments. Key CVD risk factors examined were for a subset of caregivers with complete data for these variables: blood pressure (BP), cholesterol levels, body mass index (BMI), perceived stress (Cohen’s perceived stress scale [PSS]), depression (Centers for Epidemiological Studies Depression Inventory [CESD]), and anxiety (Spielberger Trait Anxiety Inventory). Results: In the overall sample of 417 midlife caregivers, the mean age was 52±13 years, 62.1% were female, 62.1% were married, and 18% graduated from a 4-year institution. The most common care recipient was the mother of the caregiver (24.2%), 52.3% lived with their care recipient, and the average number of care hours per week was 25.13 ± 27.23. Care given included help bathing, dressing, and toileting (55.4%), shopping, cooking, laundry, and housework (88.7%), and help with transportation in and out of the home (65.2%). Data regarding CVD risk factors were available for a subset of 66 caregivers. Of those, 71.2% were either overweight or obese, mean systolic BP was 128±20, mean diastolic BP was 78±11, 57.6% had high density lipoprotein cholesterol &lt;60, low density lipoprotein &gt;100 (48.5%), 31.8% had total cholesterol &gt;200, and 13% had triglycerides &gt;150. The average score on the PSS was moderate at 22.5±6.5. Mean depressive symptom score was 8.7±7 and mean anxiety was high at 34.9±9. Conclusions: Caregivers at midlife are a unique subgroup, often caring for parents, and show unfavorable levels of CVD risk factors such as low HDL, high LDL, and high perceived stress and anxiety.
Abstract 10726: Cardiomyocyte Targeting Peptide to Deliver Amiodarone
Authors: Maliha Zahid, Beth Weber, Ray Yurko, Kazi Islam, Guy Salama
Journal: Circulation (2022)

Introduction: Amiodarone remains underutilized as an anti-arrhythmic due to significant off-target toxicities with long-term use. We hypothesized that the required dose could be minimized by targeting amiodarone to cardiomyocytes by utilizing a cardiomyocyte targeting peptide (CTP). Methods: CTP (APWHLSSQYSRT) was conjugated to amiodarone via a disulfide bond, HPLC purified, characterized by MALDI/TOF, and stability at 37°C assessed using serial HPLCs over 21 days. Adult, male guinea pigs (GP; n=4/group) were injected intraperitoneally daily with vehicle (7 days), amiodarone (7 days; 80mg/Kg), 1/10 th the molar dose of CTP-amiodarone (5 days), or CTP (5 days), followed by euthanasia, hearts excised, perfused on a Langendorff apparatus with Tyrode’s solution, and placed in a custom-designed chamber blebbistatin (5 μM) to minimize contractions. Bolus injections of voltage (RH237) and Ca 2+ -indicator dye (Rhod-2/AM) were injected to simultaneously map cardiac action potentials (APs) and Ca 2+ transients (CaT), at 610-750nm and 570-595nm, respectively with 2 CMOS cameras, followed by pacing at 250ms to measure conduction velocity (CV), AP and CaT durations (at 90% recovery). Results: CTP-amiodarone produced a single HPLC peak at 16mins that remained stable for 21 days. CTP-amiodarone and amiodarone decreased conduction velocities in myocytes significantly compared to control GPs (0.92±0.05, 0.87±0.08ms, vs. 1.00±0.03m/s respectively, p&lt;0.001). Amiodarone increased AP duration (192±5ms vs. 175±8ms for vehicle, p=0.0025), while CTP-amiodarone decreased it significantly (157±16ms, p=0.0136), similar to CTP alone (155±13, p=0.0039). Both amiodarone and CTP-amiodarone significantly decreased CaTs compared to vehicle treated GPs. CTP-amiodarone and CTP decreased CaTs to an extent greater than amiodarone alone (p&lt;0.001). Conclusions: Our data suggests that amiodarone can be stably covalently linked to CTP, which is able to deliver amiodarone to cardiomyocytes in vivo in GPs, at 1/10 th the dose of amiodarone needed to produce comparable slowing of CVs. The ability of CTP alone to decrease AP durations and CaTs was a surprise finding and merits further study to fully characterize the anti-arrhythmic actions of the CTP-amiodarone conjugate.
Abstract 10422: Sesn2 Mediates Metformin Rescued Age-Related Cardiac Dysfunctions of Cardiorenal Syndrome
Authors: Migdalia Iglesias, Di Ren, Lily Slotabec, Hao Wang, Linda Ines Zoungrana, Meredith Krause-Hauch, Ji Li
Journal: Circulation (2022)

Introduction: Cardiorenal syndrome (CRS) consists of disorders of the kidneys and heart, whereby dysfunction of one organ may induce dysfunction of the other. Acute kidney injury (AKI) leads to a reduction in blood flow and energy supply to the heart. AMP-activated protein kinase (AMPK) as an energy sensor regulates energy metabolism via interacting with a scaffold protein Sesn2. The anti-diabetes drug metformin is an AMPK agonist, and it has been reported to regulate substrate metabolism under physiological and pathological conditions. But the beneficial role of metformin in CRS remains unknown. Hypothesis: Age-related impaired AMPK signaling contributes to cardiac intolerance to AKI-induced insults in the elderly. Metformin treatment ameliorates CRS through triggering Sens2/AMPK activation. Methods: Young (3-5 months) and aged (21-23 months) C57BL/6J wild type (WT), cardiomyocyte specific knock out (cSesn2 -/- ) and littermates (Sesn2 f/f ) C57BL/6J mice were subjected to AKI with a laparotomy and the renal artery and vein were clamped for 15 min followed by 72 hr of reperfusion (IRI). Seahorse XF Analyzer for mitochondrial respirational functions. Results: The higher levels of serum creatinine were observed after IRI-induced AKI in the aged versus young WT and cSens2 -/- versus Sesn2 f/f mice. Interestingly, administration of metformin can significantly reduce serum creatinine levels by IRI-induced AKI in young/aged WT and Sesn2 f/f but not cSesn2 -/- mice. Renal histological analysis showed higher incidence of tubular necrosis in the aged versus young AKI mice, the tubular necrosis was significantly reduced in the metformin treated young and aged AKI mice. Echocardiography data showed that AKI caused cardiac systolic dysfunctions in all experimental groups, while metformin treatment improved cardiac functions of young/aged WT and Sesn2 f/f but not cSesn2 -/- mice. Moreover, metformin treatment triggered AMPK activation and improved mitochondrial respiration rate and ATP production of cardiomyocytes from young/aged WT and Sesn2 f/f but not cSesn2 -/- hearts. Conclusions: Aging augments cardiac vulnerability to IRI-induced AKI. Metformin can rescue cardiac dysfunctions and renal injury caused by AKI through Sesn2/AMPK signaling pathway.
Abstract 10489: CVSA Early Career Investigator Award Finalist: Restrictive or Liberal Transfusion for Acute Coronary Syndromes - Insights From the TRICS-III Randomized Controlled Trial, Systematic Review, and Meta-Analysis
Authors: Nikhil Mistry, Greg Hare, Nadine Shehata, Fabio Papa, Robert S Kramer, TARIT SAHA, Subodh Verma, David Mazer
Journal: Circulation (2022)

Introduction: The optimal transfusion strategy for patients with ACS is unclear. Current data are inconclusive and there is a paucity of long term data; therefore, we performed a subgroup analysis of patients with AMI in the Transfusion Thresholds in Cardiac Surgery (TRICS-III) randomized controlled trial (RCT) to add evidence addressing this important clinical question, and interpret the results in the context of a systematic review and meta-analysis. Methods: The TRICS-III trial randomized patients undergoing cardiac surgery on cardiopulmonary bypass with a moderate-to-high risk of death to restrictive transfusion (transfuse at hemoglobin &lt;7.5g/dL) or a liberal strategy (operating room and ICU: transfuse at hemoglobin &lt;9.5g/dL; ward: &lt;8.5g/dL). AMI patients were those undergoing coronary artery bypass graft surgery with a recent MI and ≥1 of the following enrichment criteria: unstable angina, critical preoperative state, preoperative intra aortic balloon pump, and/or emergency surgery. The primary outcome for this analysis was MACE (all-cause death, MI, and revascularization) at 6 months. The MEDLINE and EMBASE databases were searched through April 2022 to identify RCTs evaluating restrictive versus liberal transfusion in patients with ACS. The primary outcome was MACE at the longest available timepoint. Results: In the TRICS AMI population (N=194), a restrictive transfusion strategy did not increase the risk of MACE (OR: 1.36; 95% CI: 0.57-3.27). Three additional RCTs met eligibility criteria for the systematic review yielding a total of 1015 patients. The transfusion strategies were similar across all studies. After synthesizing the data, restrictive transfusion was associated with a trend toward an increased absolute risk of MACE (4%; 95% CI, -1 to 9%) and MI (3%; 95% CI, 0 to 6%) at the longest available timepoint (Figure). Conclusion: In the setting of ACS, liberal transfusion strategies may reduce the risk of long term adverse cardiovascular events.
Abstract 10369: Meta-Analysis of Coronary Computed Tomography versus Invasive Coronary Angiography in Stable Chest Pain
Authors: Ahmad Al-Abdouh, Mohammad As-Sayaideh, Mohammed Mhanna, Waiel Abusnina, Ahmad Jabri, mahmoud Barbarawi, Taqwa Alabduh, Usama Talib, Sireesha Upadhrasta, Timir K Paul
Journal: Circulation (2022)

Background: The coronary computed tomography angiography (CCTA) is a noninvasive alternative tool in diagnosis of coronary artery disease compared to invasive coronary angiography (ICA). However, there is uncertainty regarding its usefulness in reducing major adverse cardiovascular events in stable chest pain patients. Methods: We have searched EMBASE, PubMed, and Cochrane Library (inception through May 24 th , 2022) for randomized controlled trials (RCTs) evaluating CCTA versus ICA in stable chest pain. The Mantel-Haenszel method was used with Paule-Mandel estimator of tau 2 and Hartung-Knapp-Sidik-Jonkman adjustment (given small number of the included studies) to calculate the risk ratio (RR) and 95% confidence interval (CI). Results: Three RCTs with a total of 5,393 patients were included in this study. There was no significant difference between CCTA and ICA in terms of myocardial infarction [RR: 1.12; 95%CI: 0.60; 2.09; I 2 :0%] [Figure ], stroke [RR: 0.52; 95%CI: 0.22; 1.24; I 2 :0%], all-cause mortality [RR: 1.83; 95%CI: 0.17; 20.18; I 2 :50%], or cardiovascular mortality [RR: 0.47; 95%CI: 0.02; 9.15; I 2 :0%]. Conclusion: This meta-analysis suggests that there is no difference between CCTA and ICA for stable chest pain evaluation in terms of myocardial infarction, stroke, all-cause mortality, or cardiovascular mortality.
Abstract 10850: Epicardial Adipose Tissue is Associated With Left Atrial Volume and Fibrosis in Patients With Atrial Fibrillation
Authors: Yaacoub Chahine, Bahareh Askari-Atapour, Kirsten Kwan, Carter Anderson, Fima Macheret, Tanzina Afroze, Savannah Bifulco, Matthew D Cham, Karen G Ordovas, Patrick M Boyle, Nazem W Akoum
Journal: Circulation (2022)

Background : Obesity is a risk factor for atrial fibrillation (AF) and strongly influences response to treatment. Atrial fibrosis shows similar associations. Epicardial adipose tissue (EAT) may be a link between these associations. We sought to assess whether EAT is associated with body mass index (BMI), left atrial (LA) volume and fibrosis. Methods: LA fibrosis and EAT were assessed using Late Gadolinium Enhancement, and Dixon MRI sequences, respectively. We derived 3D models incorporating fibrosis and EAT to assess spatial colocalization: we measured the distance of fibrotic and non-fibrotic areas to the nearest EAT, and calculated the volume of EAT within a radius of 5 mm for every LA surface point. Results: 103 AF patients (64% paroxysmal, 73% male) were analyzed. LA volume index was 54.9 [41.2, 69.7] mL/m 2 , LA EAT index was 17.4 [12.7, 22.9] mL/m 2 , and LA fibrosis was 17.1 [12.4, 23.1] %. LA EAT was significantly correlated with BMI (R=0.557, p&lt;0.001); as well as with LA volume and LA fibrosis after BSA adjustment (R=0.579 and R=0.432 respectively, p&lt;0.001 for both) (Panel A). Multivariable analysis showed LA EAT to be independently associated with LA volume and fibrosis. Aggregation of local EAT proximity values in all models revealed that the minimum distance to fat was significantly greater for fibrotic LA surface regions compared to non-fibrotic areas (6.97 mm [3.28, 12.13] vs 5.71 mm [2.58, 10.35], p&lt;0.001) (Panel C). The proportion of LA surface points having fat within a radius of 5 mm was greater for non-fibrotic compared to fibrotic regions (37.6% [23.4, 48] vs 41.6% [31.2, 58.1] respectively, p=0.021). Thus, 3D registration of fat and fibrosis around the LA showed no clear spatial overlap between EAT and fibrotic LA regions (Panel B). Conclusion: LA EAT is associated with obesity (BMI) as well as LA volume and fibrosis. Regions of LA EAT are not colocalized with fibrotic areas, suggesting a systemic or paracrine mechanism rather than EAT infiltration of fibrotic areas.
Abstract 10040: Impact of Periaortic Adipose Tissue Detected by Computed Tomography on Aortic Vulnerable Plaques Identified by Non-Obstructive General Angioscopy
Authors: Yutaka Koyama, Keisuke Kojima, Kurara Takahashi, Shohei Migita, Masatsugu Miyagawa, Yudai Tanaka, Hidesato Fujito, Akihito Ohgaku, Yasunari Ebuchi, Riku Arai, Masaki Monden, Katsufumi Fukumoto, Norio Takei, Nobuhiro Murata, Daisuke Fukamachi, Yasuo Okumura
Journal: Circulation (2022)

Introduction: Periaortic adipose tissue (PAAT) is related to the development of cardiovascular disease. However, the relationship between periaortic adipose tissue (PAAT) and aortic plaque instability has not been elucidated. Hypothesis: We hypothesized that PAAT would be associated with aortic vulnerable plaques derived non-obstructive general angioscopy (NOGA) in patients with cardiovascular disease. Methods: We investigated 117 patients who underwent NOGA of the aorta and CT. PAAT volume was measured using the volume-rendering method by extracting the area from -30 to -190 HU within the thoracic aorta. PAAT volume index (PAAT-I) was defined as PAAT volume divided by the body surface area. We evaluated the number of vulnerable plaques including ruptured plaques, ulcerations, thrombi, intense yellow plaques by NOGA in the whole aorta. All patients were divided into the median value of PAAT-I (16.9 [13.0 - 21.6] ml/m2) Results: The high PAAT-I patients had significantly greater number of vulnerable plaques in the thoracic aorta than the low PAAT-I patients (2 [1-4] vs 1 [0-3], p&lt;0.05). The PAAT-I had a correlation with the number of vulnerable plaques in the thoracic and whole aorta (r=0.44, p&lt;0.001, r=0.35, p&lt;0.01, respectively) Conclusions: PAAT in the thoracic aorta was related to the number of NOGA derived-aortic vulnerable plaques in patients with cardiovascular disease. PAAT may play an important role in the development of aortic plaque instability.
Abstract 10111: Efficacy and Safety of Tafolecimab in Chinese Patients With Non-Familial Hypercholesterolemia (CREDIT-1): A 48-Week Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial
Authors: Yong Huo, Yong Li, Ping Zhang, Huan Deng, Haoyu Li, Pei An, Fengtai Xue, Zhongxun Yu, Qingyang Ma, Litong Qi, Beijian Chen, Qiufang Lian, Shuqing Wang, Di Lu, LEI QIAN
Journal: Circulation (2022)

Introduction: Currently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies demonstrated robust low density lipoprotein cholesterol (LDL-C)-lowering efficacy at doses up to 420 mg monthly, while longer dosing intervals are largely unexplored. We assessed the efficacy and safety of tafolecimab, a potential long-acting fully human PCSK9 monoclonal antibody, in Chinese patients with non-familial hypercholesterolemia (ClinicalTrials.gov, NCT04289285). Methods: Patients were randomized 2:2:1:1 to receive subcutaneous tafolecimab 450 mg every 4 weeks (Q4W), tafolecimab 600 mg every 6 weeks (Q6W), placebo Q4W or placebo Q6W for 48 weeks. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. Secondary endpoints included proportion of patients achieving ≥50% LDL-C reductions, LDL-C &lt;1.8 mmol/L and LDL-C &lt;1.4 mmol/L. Results: A total of 618 patients (mean LDL-C level 2.85 mmol/L; 9.3% on ezetimibe; 72.8% at very-high cardiovascular risk) were randomized. Of 614 patients receiving at least one dose of the study treatment, 568 (92.5%) completed the study. At both dose regimens, tafolecimab treatment induced significant reductions in LDL-C levels, and significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C &lt;1.8 mmol/L and LDL-C &lt;1.4 mmol/L compared with corresponding placebo groups ( Table ). Meanwhile, significant reductions in non-high density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) levels were achieved with tafolecimab versus placebo at week 48. The most commonly-reported treatment-emergent adverse events were upper respiratory tract infection, urinary tract infection and hyperuricemia. Conclusions: Tafolecimab administered at either 450 mg Q4W or 600 mg Q6W yielded significant and durable reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with non-familial hypercholesterolemia.
Abstract 11020: Predictors of Cardiac Arrest Including Ventricular Fibrillation in Young Patients Hospitalized With Hypertrophic Obstructive Cardiomyopathy: An Artificial Neural Network Analysis Using a Nationwide Cohort
Authors: Aditi K Bhanushali, Aneri Patel, Mounika Pusa, Sanjana Aggarwal, Muhammad Saad Siddique, Haris Javed, Harsh R Sura, RITIKA DHRUVE, Marisha Rai Sharma, Rupak Desai
Journal: Circulation (2022)

Background: It is crucial for providers to screen for high-risk patients with limited data being available on young hypertrophic obstructive cardiomyopathy (YHOCM) patients. We aimed to determine predictors of cardiac arrest including ventricular Fibrillations (VF) in this population using the Artificial Neural Network (ANN) model in a national cohort. Methods: We identified young patients (18-44 years) with HOCM from National Inpatient Sample (2018) with relevant ICD 10 codes. ANN’s predictive factors were selected for cardiac arrest including VF. YHOCM were randomly split between training (70.8%) and testing (29.2%) datasets. Training data was used to calibrate ANN whereas testing data was used to evaluate the accuracy of the algorithm. We compared the frequency of incorrect prediction between training and testing data and measured area under the Receiver Operating Curve (AUC) to determine ANN’s efficacy in predicting cardiac arrest. Results: YHOCM (2280, median age 36 years, 52.4% males, 47.6% females, 50.9% Whites, 32.2% Blacks, 11.6% Hispanics) had all-cause mortality of 21.1% with compared to that of 1.1% without cardiac arrest. Training data showed a lower rate of 3.9% vs 4.7% of error in predictions vs testing, thereby depicting better accuracy. Normalized predictors are displayed in Fig 1a. The AUC was 0.799 (Fig. 1b) which shows an excellent ANN model for cardiac arrest in YHOCM hospitalizations. Conclusions: Our ANN model successfully revealed predictors of cardiac arrest including VF in YHOCM patients that can be utilized to improve/prevent such events in high-risk patients leading to a better quality of life and survival rates.
Abstract 11021: Chest Symptoms and Subsequent Risk of Incident Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Kentaro Ejiri, Yejin Mok, Ning Ding, Patricia Chang, Wayne D Rosamond, Amil M Shah, Pamela L Lutsey, Lin Y Chen, Michael J Blaha, Lena Mathews, Kuni Matsushita
Journal: Circulation (2022)

Introduction: The 2021 AHA/ACC Chest Pain Guideline classifies the likelihood of ischemia according to chest symptom characteristics. However, the associations of various chest symptoms with long-term risk of different cardiovascular disease (CVD) have not been fully investigated. Aim: To quantify the associations of chest pain and dyspnea with incident major CVD. Methods: In 13,200 ARIC participants (mean age 54 [SD 6] years, 56% female, 25% Blacks) without prior CVD at visit 1 (1987-89), we categorized chest pain into definite angina, possible angina, non-anginal chest pain, and no chest pain based on the WHO Rose questionnaire, and dyspnea into grade 0, 1, 2, and 3-4 based on the Medical Research Council scale. CVD outcomes included myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), and ischemic stroke (median follow-up, 26-28 years). We estimated 30-year cumulative incidence accounting for competing risk of deaths and ran multivariable Cox models. Results: Definite angina and possible angina were robustly associated with incident MI (Table), with adjusted HR 1.83 (95%CI 1.51-2.22) and 1.64 (1.26-2.13), respectively. These two chest pain types were also related to HF, AF, and ischemic stroke, although possible angina did not reach statistical significance for stroke. Even non-anginal chest pain was associated with MI, HF, and AF. Dyspnea showed graded association with all CVD outcomes, but particularly with MI and HF (bottom half of Table). For example, grade 3-4 and 2 showed HR of 2.13 (1.71-2.65) and 1.41 (1.13-1.76), respectively, for MI. When chest pain and dyspnea were modeled simultaneously, their associations were independent. Conclusions: In persons without prior CVD, chest pain and dyspnea were independently associated with different CVD events over 30 years. Our findings suggest broad prognostic implications of chest pain beyond coronary disease and emphasize the importance of recognizing dyspnea for CVD risk management.